Microvascular responses to hemodilution with Hb vesicles as red blood cellsubstitutes: influence of O-2 affinity

Phospholipid vesicles encapsulating purified hemoglobin (HbV) were develope d to provide O-2-carrying capacity to plasma expanders. Microvascular perfu sion was determined for HbV with different O-2 affinity (P-50 = 9, 16, and 30 mmHg) prepared by coencapsulating pyridoxal 5'-phosphate (PLP) at the mo lar ratios of[PLP]/[Hb] = 0, 0.5, and 3, respectively (cf. hamster blood, P -50: 28 mmHg), and suspended in 8 g/dl human serum albumin (HSA). Eighty pe rcent of the red blood cell (RBC) mass of conscious Syrian golden hamsters fitted with dorsal skinfold windows was substituted with either of the HbV- HSA suspensions, washed hamster RBC suspended in HSA(RBC-HSA), and HSA alon e. All three HbV-HSA groups and RBC-HSA groups showed stable blood pressure and heart rate, which could not be sustained with HSA alone. Only the HbV (P-50 = 9)-HSA group showed an increase in arterial O-2 tension (89.8 +/- 1 4.7 mmHg, baseline 58.4 +/- 4.0 mmHg) because of hyperventilation, and micr ovascular perfusion was decreased, indicating that facilitated O-2 unloadin g of HbV by decreasing the O-2 affinity (increasing P-50) with PLP as an al losteric effector is important. Microvascular perfusion and microvascular a nd interstitial O-2 tensions in the HbV (P-50 = 16 and 30)-HSA groups were significantly higher than those in the HSA group. The O-2 release rate from the HbV was 18-32 s(-1) vs. 4.4 s(-1) for RBC. Functional capillary densit y was improved from 17 to 41% on average by decreasing P-50 from 30 to 16 m mHg, which appears to be an optimal value for the P-50 in this system.